The preparation of glucagon derivatives and analogues suitable for structure-function studies of the peptide hormone will be investigated. A primary goal will be the preparation of glucagon analogues which will act as an antagonist (competitive inhibitor) to the hormone for potential treatment of hyperglycemia in diabetes, and for studying the mechanism of glucagon hormone action. Other desirable properties for these compounds include analogues which are more active than the hormone itself or are partial agonists, radiolabeled derivatives which are suitable for binding studies with the all membrane receptors of the hormone and for degredation studies in vivo, and analogues which are longer lasting than the native hormone. Studies of the conformational and dynamic properties of interesting analogues will be made and the results compared with those of glucagon. Glucagon analogues possessing potential affinity labeling groups will be synthesized and used to study glucagon membrane receptors and the associated receptor-adenylate cyclase system.